Systemic immune responses to anterior chamber antigens are deviant in that certain types of immune effectors (delayed hypersensitivity and complement fixing antibodies) are selectively deleted and/or suppressed, whereas other effectors (cytotoxic T cells, non-complement fixing antibodies) are induced. This unique pattern of immune effectors has been termed Anterior Chamber Associate Immune Deviation (ACAID). Since it has been determined that anatomic integrity of he antigen-containing eye and the spleen is required for ACAID induction during the first 4-5 days after intracameral antigen injection of antigen, experiments have been designed to investigate the cellular and molecular bases of these requirements. Two related hypotheses will be tested experimentally: (1) A qualitatively and/or quantitatively distinct antigen-specific ACAID-inducing signal escapes into the blood from eyes into which antigen has been introduced; (2) In the spleen, the ACAID-inducing signal preferentially activates TH2 cells, which in turn impair the induction of TH1 cells that are responsible for the generation of delayed hypersensitivity and complement fixing antibodies. Recent evidence indicates that expression of immunity within the eye may also be abnormal. A third hypothesis to be tested is Local intraocular factors (cells and molecules) act to reduce intraocular expression of delayed hypersensitivity. Since alterations in induction and expression of immunity toward intraocular antigens exist, a fourth hypothesis to be tested states that Deviant immune responses (ACAID) may have beneficial or deleterious effect in the eye, leading to immune-related ocular disease. To test these hypotheses, we have devised four Specific Aims: 1. Study of the eye as a source of the ACAID-inducing signal. 2. Analyze splenic T cells to identify and study regulatory lymphocytes in ACAID. 3. Characterize immune effector cell responses in the anterior chamber of the eye. 4. Explore the possible relationships between ACAID and experimental ocular diseases. As new data accumulate concerning the unique relationship between the systemic immune system and the eye, progress should be possible in our understanding of the etiology of ocular disease in which the immune system plays an important pathogenic role. Based on this understanding, strategies can then be devised to manipulate the immune system in specific ways designed to prevent and/or treat immunopathogenic ocular diseases.